Exposure to drug-associated cues evokes drug-seeking behavior and is regarded as a major cause of relapse. Cues evoke burst firing of ventral tegmental area (VTA) dopamine (DA) neurons and phasic DA release in the nucleus accumbens (NAc). Cholinergic and glutamatergic input to the VTA is suggested to gate phasic DA activity. However, the role of VTA cholinergic and glutamatergic receptors in regulating phasic dopamine release and cue-induced drug-seeking in cocaine experienced subjects is not known. In male Sprague-Dawley rats, we found that VTA inactivation strongly inhibited, while VTA stimulation promoted, cocaine-seeking behavior during early withdrawal. Blockade of phasic activated D1 receptors in the NAc core also strongly inhibited cue-induced cocaine-seeking - suggesting an important role of phasic DA activity in the VTA to NAc core circuit. Next, we examined the role of VTA acetylcholine receptors (AChRs) and N-methyl-D-aspartate receptors (NMDARs) in regulating both NAc core phasic DA release and cue-induced cocaine-seeking. In cocaine naïve subjects, VTA infusion of the nicotinic acetylcholine receptor (AChR) antagonist mecamylamine, the muscarinic AChR antagonist scopolamine, or the NMDAR antagonist AP-5, led to robust attenuation of phasic DA release in the NAc core. During early cocaine withdrawal, VTA infusion of AP-5 had limited effects on NAc phasic DA release and cue-induced cocaine-seeking while VTA infusion of mecamylamine or scopolamine robustly inhibited both phasic DA release and cocaine-seeking. The results demonstrate that VTA AChRs, but not NMDARs, strongly regulate cue-induced cocaine-seeking and phasic DA release during early cocaine withdrawal.

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a cesarean delivery in a woman with a high-risk pregnancy is twofold (aOR 1.99, CI 1.92-2.06) if she is cared for in a hospital within the high-cesarean-delivery-rate group than in one within the low/mid-cesarean-delivery-rate group. Meanwhile, we found no significant difference in neonatal outcomes or maternal outcomes between patients delivered in a high vs. low-cesarean-delivery-rate hospital. CONCLUSION: Individual hospitals are in themselves independent risk factors for cesarean delivery, regardless of hospital location, payment source, teaching status and bed size, and regardless of patients' pregnancy risks and characteristics. Choosing to give birth in a certain hospital can put patients at a twofold risk of having a cesarean delivery, without benefits in maternal or neonatal outcomes.

OBJECTIVE: Oxytocin is one of the most frequently used agents in obstetrics. It is generally considered to be safe and effective for induction and augmentation of labor but has been implicated in uterine hyperstimulation and adverse fetal outcomes. However, the management of labor with oxytocin in response to changes in fetal status remains an area of debate. This study sought to assess the costeffectiveness of reducing or ceasing oxytocin administration in response to category II fetal heart rate tracings during induction of labor. STUDY DESIGN: A decision-analytic model was built using TreeAge software with probabilities, costs and utilities derived from the literature. Primary outcomes included: cerebral palsy (CP), neonatal mortality, and mode of delivery. Secondary outcomes included: cost per quality-adjusted life year (cost-effectiveness threshold set at $100,000/quality-adjusted life year (QALY), admission to the NICU, low 5 minute Apgar score (<7). Sensitivity analyses were performed to determine the robustness of our baseline assumptions. RESULTS: In a theoretical cohort of 900,000 women, representing the estimated number of women undergoing induction at term in the U.S., decreasing or stopping oxytocin in response to category II tracings for patients undergoing induction of labor prevented 12,510 NICU admissions, 4,410 low Apgar scores, 204 neonatal deaths, and 126 cases of cerebral palsy (Table). However, there were 81,900 more cesarean deliveries. The strategy cost $347 million more, but was cost-effective with an ICER of $8,680 per QALY. Sensitivity analysis revealed that the intervention would be cost-effective up to a cesarean rate of 55.1%. CONCLUSION: Decreasing or stopping oxytocin in response to category II fetal heart rate tracings is cost-effective. This intervention increases the rate of cesarean deliveries but reduces neonatal morbidity and mortality. Further work on this guideline should be performed to ascertain how the approach using different aspects of the category II tracing to guide care might lead to similar improved outcomes without increasing the cesarean delivery rate.

INTRODUCTION: Oxytocin is generally considered to be safe and effective for induction and augmentation of labor, but has been implicated in uterine hyperstimulation and adverse fetal outcomes. The management of labor with oxytocin in response to changes in fetal status is in need of additional consensus guidelines. This study sought to assess the cost-effectiveness of implementing an oxytocin in-use checklist. METHODS: A decision-analytic model was built using TreeAge with probabilities, costs and utilities derived from the literature. Primary outcomes included: Cerebral Palsy, neonatal mortality, and mode of delivery. Secondary outcomes included: cost per quality-adjusted life year (cost-effectiveness threshold set at $100,000/quality-adjusted life year, NICU admission, and low 5 minute Apgar score (< 7). Sensitivity analyses were performed to determine the robustness of our baseline assumptions. RESULTS: In a theoretical cohort of 900,000 women, representing the estimated number of women undergoing induction at term in U.S., implementing the in-use checklist for women undergoing induction with oxytocin at term was a cost-effective strategy. Use of the checklist prevented 13,140 NICU admissions, 1,080 low Apgar scores, 50 neonatal deaths, 27,000 cesarean deliveries, and 30 cases of cerebral palsy. Sensitivity analysis revealed that the strategy is also cost-saving if the checklist costs less than #304 per delivery. Estimated cost of the checklist was $35 per delivery. CONCLUSION: Standardizing oxytocin administration with an in-use checklist is both cost-effective and cost-saving. Most importantly, it reduces neonatal and maternal morbidity and mortality. Examination of both how to translate the use of such checklists and improve their impact deserves further attention.

Background Oxytocin is one of the most frequently used medications in obstetrics. It is generally considered to be safe and effective for induction and augmentation of labor but has been implicated in uterine hyperstimulation and adverse fetal outcomes. The management of labor with oxytocin in response to changes in fetal status remains an area of debate. Objective This study sought to assess the cost-effectiveness of reducing or ceasing oxytocin administration in response to Category II fetal heart rate tracings. Study Design A decision-analytic model was built using TreeAge 2016 software (TreeAge Software Inc.) with probabilities, costs, and utilities derived from the literature. Primary outcomes included cerebral palsy (CP), neonatal mortality, and mode of delivery. Secondary outcomes included cost per quality-adjusted life year (QALY; cost-effectiveness threshold set at $100,000/QALY), admission to the neonatal intensive care unit (NICU), and low 5-minute Apgar score (<7). Sensitivity analyses were performed to determine the robustness of our baseline assumptions. Results In a theoretical cohort of 900,000 women (estimated number of women undergoing induction at term in the United States), decreasing or stopping oxytocin in response to Category II tracings prevented 12,510 NICU admissions, 4,410 low Apgar scores, 204 neonatal deaths, and 126 cases of CP. However, there were 81,900 more cesarean deliveries. The strategy cost $356 million more, but was cost-effective with an ICER of $9,881.5 per QALY. Sensitivity analysis revealed that the intervention would be cost-effective up to a cesarean rate of 54%. Conclusion Decreasing or stopping oxytocin in response to Category II fetal heart rate tracings is cost-effective. This intervention increases the rate of cesarean deliveries but reduces neonatal morbidity and mortality. Further work on this guideline should be performed to ascertain how the approach using different aspects of the Category II tracing to guide care might lead to similar improved outcomes without increasing the cesarean delivery rate.

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